Two-way text message interventions and healthcare outcomes in Africa: Systematic review of randomized trials with meta-analyses on appointment attendance and medicine adherence

Background The growing access to mobile phones in Africa has led to an increase in mobile health interventions, including an increasing number of two-way text message interventions. However, their effect on healthcare outcomes in an African context is uncertain. This systematic review aims to landscape randomized trials involving two-way text message interventions and estimate their effect on healthcare outcomes. Methods We searched Medline, Embase, Cochrane Central Register of Controlled Trials, The Global Health Library (up to 12 August 2021) and trial registries (up to 24 April 2020). Published and unpublished trials conducted in Africa comparing two-way text message interventions with standard care and/or one-way text message interventions were included. Trials that reported dichotomous effect estimates on healthcare appointment attendance and/or medicine adherence were assessed for risk of bias and included in meta-analyses. Results of other outcomes were reported descriptively. Results We included 31 trials (28,563 participants) all set in Sub-Saharan Africa with a wide range of clinical conditions. Overall, ten different trials were included in the primary meta-analyses, and two of these had data on both medicine adherence and appointment attendance. An additional two trials were included in sensitivity analyses. Of the 12 included trials, three were judged as overall low risk of bias and nine as overall high risk of bias trials. Two-way text messages did not improve appointment attendance, RR: 1.03; 95% CI: 0.95–1.12, I2 = 53% (5 trials, 4374 participants) but improved medicine adherence compared to standard care, RR: 1.14, 95% CI: 1.07–1.21, I2 = 8% (6 trials, 2783 participants). Conclusion Two-way text messages seemingly improve medicine adherence but has an uncertain effect on appointment attendance compared to standard care. Systematic review registration PROSPERO CRD42020175810.


Random sequence generation (selection bias)
Low risk "Random allocation was achieved through a computer-generated simple randomization scheme.» Allocation concealment (selection bias) Low risk «the participants were randomly allocated to intervention and control groups by the database administrator.» Blinding of participants and personnel (performance bias)

Low risk
Single-blind. "The investigators, data manager, research assistants, counselors, and other project staff were blinded throughout the study.»

Blinding of outcome assessment (detection bias)
Low risk "The independentmedical internet technology firm was responsible for randomization of participants and the management of sending SMS to the participants and collecting responses from them. After the scientific review had been completed, at the point of analysis, a list of participants' unique identifiers in two groups was sent to the data analysts without specifyingwhichwas the investigation group and which was the control group."

Incomplete outcome data (attrition bias)
Low risk "The study lost three participants to follow-up (two after the first visit, one after the third visit) while 209 adolescents completed the research. There was no statistically significant difference in the major demographic characteristics (age, gender, and education) between those who completed the study and those who did not."

Selective reporting (reporting bias)
Low risk Protocol registered at clinicaltrials.gov in 2018 (NCT03394391). All specified outcomes in protocol reported in article.

Bobrow 2016 Bias
Outcome: Adherence Authors' judgement Support for judgement

Random sequence generation (selection bias)
Low risk "A software algorithm assigned participants independently of the research team to informationonly adherence support, interactive adherence support, or usual care in a 1:1:1 ratio using a nondeterministic minimization algorithm to ensure balance between groups with respect to age, sex, baseline SBP, years with hypertension, and recent clinic attendance" Allocation concealment (selection bias) Unclear "All trial staff were masked to treatment allocation" Blinding of participants and personnel (performance bias) Low risk "Researchers and clinicians were not aware of randomization assignment, were trained not to ask patients about the content of messages, and were unable to determine randomization group from casual comments by participants" Blinding of outcome assessment (detection bias) Low risk "Blood pressure at 12 months from baseline measured with a validated oscillometric device. Blood pressure measurements were automated, and data were captured directly to the trial database. Trial statisticians, researchers, clinic staff, and research assistants who collected outcome data were masked to allocated interventions until the trial database was locked" Incomplete outcome data (attrition bias) Low risk "92% outcome data. Attrition rates did not differ significantly between groups. All analyses were performed on an intention-to-treat basis, and outcomes were analysed using a mixed effect model. The model was adjusted for baseline systolic blood pressure and minimization factors. "

Outcome: Adherence
Authors' judgement Support for judgement

Random sequence generation (selection bias)
Unclear risk "Cluster randomization stratified by high volume and medium and low volumes". "A volumestratified sampling method was applied to ensure inclusion of a representative sample of types of health facilities among the remaining facilities. All health facilities were randomly allocated to be an intervention or control site, stratified by high volume (hospitals) and medium and low volumes (health centers and dispensaries)." Method of randomization not described.

Allocation concealment (selection bias)
Unclear risk Not described. Blinding of participants and personnel (performance bias)

Unclear risk
Not described.

Blinding of outcome assessment (detection bias)
High risk "Women underwent structured interviews at four visits to record self-reported adherence to antiretrovirals in the past week, number and mode of communication between the participant and health workers, time and place of delivery, infant feeding practices, and any intervening clinical outcomes." Was not blinded.

Incomplete outcome data (attrition bias)
High risk "Estimation adjusted effects by logistic regression. Loss to follow up >10%" Higher proportion of people loss to follow-up in control group than intervention group (5 % more)

Selective reporting (reporting bias)
Low risk "The study has been registered on ClinicalTrials.gov under the identifier NCT01645865." Data on all outcomes specified in the protocol are reported in article.

Leiby, 2016 Bias Outcome: Attendance
Authors' judgement Support for judgement Random sequence generation (selection bias) Unclear risk "Patients were randomly assigned to one of the 3 study arms". "The study sample was stratified by district (Lusaka or Chongwe), age (<18 or >18), and self-reported VMMC intention (within 2 months or not)." Method of randomisation not described.

Allocation concealment (selection bias)
Unclear risk Not described

Blinding of participants and personnel (performance bias)
Unclear risk "Participants were anonymous (numbers in platform). Subscriber phone numbers are not accessible to the counsellors or program managers, making the platform strictly confidential" No additional information about blinding of participants or personnel.

Blinding of outcome assessment (detection bias)
High risk "The main method for collecting information from participants was SMS surveys + field team collected limited data (procedure date, partial phone numbers, age, and neighbourhood) from client intake forms."

Selective reporting (reporting bias))
High risk Protocol submitted to the Registry for International Development Impact Evaluations in 2014. Not all specified secondary outcomes in protocol are listed in the article.

Lester, 2010 Bias Outcome: Adherence
Authors' judgement Support for judgement

Random sequence generation (selection bias)
Low risk "Individually randomised, parallel multisite controlled trial. Simple randomisation (1:1). A project statistician generated the randomisation numbers with a random number generating program."

Allocation concealment (selection bias)
Low risk "Written allocation of assignment was sealed in individual opaque envelopes marked with study identification numbers, which were distributed to all three study clinics."

Blinding of participants and personnel (performance bias)
Low risk "Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation, study participants and clinic staff were not masked to treatment."

Blinding of outcome assessment (detection bias)
Low risk "Women underwent structured interviews at four visits to record self-reported adherence to antiretrovirals in the past week, number and mode of communication between the participant and health workers, time and place of delivery, infant feeding practices, and any intervening clinical outcomes." Was not blinded.

Incomplete outcome data (attrition bias)
Low risk «The analysis of primary outcomes was by intention to treat. The primary analyses were not adjusted, as prespecified and recommended. We also did a per-protocol (complete-case) analysis of the primary outcomes, in which only participants who had complete primary outcome data (selfreported adherence at 6 and 12 months and viral load at 12 months) were included. Heterogeneity of the effect of the intervention across subgroups was assessed by comparing logistic regression models with and without interaction term between treatment allocation and subgroup-defining variables» Loss to follow up is <95% in both intervention and control groups.

Selective reporting (reporting bias)
High Outcomes with reported results in article: Primary outcome and all-cause mortality. Reported in article that all other pre-specified outcomes will be reported separately.

Lund, 2014 Bias Outcome: Adherence
Authors' judgement Support for judgement

Random sequence generation (selection bias)
Unclear risk "Pragmatic cluster-randomised controlled trial. Primary healthcare facilities were assigned by simple random allocation to the mobile phone intervention. Stratified by district." Method of randomisation not described.

Allocation concealment (selection bias)
Unclear risk Not described.

Blinding of participants and personnel (performance bias)
High risk "Neither study participants nor clinic staff were masked because of the nature of the intervention"

Blinding of outcome assessment (detection bias)
High risk "The selected primary health care facility staff also functioned as research assistants. Clinical staff was not blinded"

Selective reporting (reporting bias)
High risk Protocol retrospectively registered in Clingov: NCT01821222 published 2013, study start 2009. All specified outcomes in protocol, reported in article.

Allocation concealment (selection bias)
Low risk "The allocation codes were then sequentially affixed to the phone numbers of consecutively recruited participants by trained research staff at the YCH ATC. This sequence was sent to the research centre by email, and concealed in a password-protected computer until interventions were assigned"

Blinding of participants and personnel (performance bias)
Low risk "From the point of enrolment, patients were identified only by their phone numbers and their sequential trial numbers. The interviewers transmitted the phone numbers of the enrolees to the research staff. The research staff responsible for allocation had access to the allocation codes and the phone numbers of participants. The program secretary responsible for sending the text messages received the allocations (SMS or No SMS) and corresponding phone numbers weekly. Only the participants were aware of their allocation."

Blinding of outcome assessment (detection bias)
Low risk "Adherence measured with VAS. Trained interviewers -blinded to group allocationcollected data using a pre-tested data collection form containing sociodemographic data, clinical information and adherence rates at baseline, 3 and 6 months" Single blinded, data analyst blinded.

Incomplete outcome data (attrition bias)
Low risk "Intention-to-treat analysis. We also used multiple imputation techniques to handle missing data. Variables for which there was too much missing data to perform imputation were excluded from the analysis but are reported (CD4-T-lymphocyte cell count and viral load). All outcome variables had some degree of missing data ranging from 0 to 35%. Multiple imputation was used to create a new data set which was the average of five data sets of imputed values. This final data set was used for all analyses." No difference in attrition in intervention and control group.

Selective reporting (reporting bias)
Low risk All ways of measuring outcome were reported. All specified outcomes in protocol reported in article.

Random sequence generation (selection bias)
Unclear risk "The protocol for treatment assignment entailed assigning every other survey to the SMS treatment group on the day of the baseline survey. To ensure that none of the survey staff would know who were chosen to receive the SMS, the study manager, who did not have any interaction with participants, randomly assigned surveys into the treatment group after the surveys were returned to the study office each day." "Privately owned pharmacies and proprietary and patent medicine vendors (PPMVs) were initially randomly selected from the numerated sites within four local government areas and enrolled into the study." The method of randomisation is not described.

Allocation concealment (selection bias)
Unclear risk Not describes

Blinding of participants and personnel (performance bias)
Low risk «To ensure that none of the survey staff would know who were chosen to receive the SMS, the study manager, who did not have any interaction with participants, randomly assigned surveys into the treatment group after the surveys were returned to the study office each day.»

Blinding of outcome assessment (detection bias)
Low risk Self-reported outcome. Survey staff blinded.

Incomplete outcome data (attrition bias)
Low risk "Primary analysis estimates the intention-to-treat effect. Adjusted for unbalance across groups.

Random sequence generation (selection bias)
Low risk "An independent biostatistician at the University of Washington's Center for AIDS Research generated the randomization sequence and assigned clusters to intervention start periods. Randomization was stratified by clinic volume and experience level."

Allocation concealment (selection bias)
Unclear risk " In a pragmatic, cluster-randomized, steppedwedge trial with 2 time periods of observation, we randomly allocated 10 clinics to begin implementing the intervention immediately and 10 clinics to begin implementing 6 months later." "An independent biostatistician (…) assigned clusters to intervention start periods". Concealment not described.

Blinding of participants and personnel (performance bias)
High risk "Due to the nature of the intervention and the need to inform facilities of their participation, it was not possible to blind clusters, healthcare providers, investigators, data analysts, or individual participants to group assignments" Blinding of outcome assessment (detection bias) High risk "Due to the nature of the intervention and the need to inform facilities of their participation, it was not possible to blind clusters, healthcare providers, investigators, data analysts, or individual participants to group assignments" Selective reporting (reporting bias) Low risk Protocol registered at clinicaltrials.gov in 2015.
(NCT02350140). All specified outcomes in protocol reported in article.